Oxidative changes of lens proteins are thought to occur with aging and to contribute to the development of cataracts. The goals of this project are to determine (1) the extent of oxidative modification of crystallins and metabolic enzymes in both normal and cataractous lenses, (2) the nature of the modifications and mechanisms leading to the changes, and (3) the effect of the modifications the structure and function of lens proteins. Bovine and rat lenses are used. The approach is to study the modifications of lens proteins after treatment in vitro by metal-catalyzed oxidation systems. Studies on fetal bovine lenses demonstrated that copper and iron are not associated with any crystallin to any appreciable extent in vivo. In vitro, copper appears to interact specifically with some of the bovine gamma-crystallins, and iron at greater than stoichiometric levels induces protein aggregation. These results support the possibility that metal-catalyzed oxidative reactions may contribute to age-related changes in lens. A protein that presumably protects against metal-catalyzed oxidation in cells has been identified in bovine and rat lens. Human lens proteins have been analyzed by two-dimensional polyacrylamide gel electrophoresis and many have been identified by protein sequencing and by immunoblotting.